Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications: Effect of timing, dosage, and infarct location

Abstract

To determine 1) whether the effect of intravenous nitroglycerin (NG) therapy during acute myocardial infarction on creatine kinase infarct size is influenced by infarct location (anterior vs. inferior), timing (therapy <4 hours vs. ≥4 hours after onset of pain), and dose response (mean blood pressure ≥80 mm Hg vs. <80 mm Hg during the first 12 hours) and 2) whether NG therapy modifies infarct expansion, 310 patients were randomly allocated to NG (n = 154) and control (n = 156) groups. NG infusion was titrated to lower mean blood pressure by 10% in normotensive and 30% in hypertensive patients, but not below 80 mm Hg, and was maintained for 39 hours. Measurements included clinical variables, creatine kinase infarct size (geq) as well as left ventricular (LV) asynergy, LV ejection fraction, expansion index, and thinning ratio on serial two-dimensional echocardiography. Compared with controls, creatine kinase infarct size was less in the NG group (41 vs. 55 geq, p < 0.001), in anterior (44 vs. 58 geq, p < 0.05), and inferior (39 vs. 53 geq, p < 0.025) NG subgroups, and in early than late NG subgroups (43% vs. 22% decrease). Other indexes of infarct size also improved (p ≤ 0.05) with NG compared with controls. Thus, by 10 days, LV asynergy was 40% less, LV ejection fraction was 22% more, and Killip class score was 41% less. A negative effect of mean blood pressure <80 mm Hg with NG was reflected in these indexes. In addition, expansion index increased (p < 0.001) by 31% and thinning ratio decreased (p < 0.001) by 17% in controls by 10 days but remained unchanged with NG. Infarct-related major complications were less frequent in the NG than the control groups: infarct expansion syndrome (2% vs. 15%, p < 0.0005), LV thrombus (5% vs. 22%, p < 0.0005), cardiogenic shock (5% vs. 15%, p < 0.005), and infarct extension (11% vs. 22%, p < 0.025). Mortality was less in NG than in control groups in-hospital (14% vs. 26%, p < 0.01), at 3 months (16% vs. 28%, p < 0.025) and 12 months (21% vs. 31%, p < 0.05), but this advantage was only found in the anterior subgroups. The results indicate that NG therapy in acute myocardial infarction limits indexes of infarct size, infarct expansion, and major infarct-related complications independent of infarct location. Greater benefit on infarct size occurs with early timing and target mean blood pressure ≥80 mm Hg.